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Comparative Study
. 2024 Nov 1;79(11):glae230.
doi: 10.1093/gerona/glae230.

Black Americans With Sickle Cell Disease (SCD) Demonstrate Accelerated Epigenetic Pace of Aging Compared to Black Americans Without SCD

Melanie E Garrett  1 , Brandon Le  1 , Kyle J Bourassa  2   3 , Michelle F Dennis  2   4 , Daniel Hatch  5 , Qing Yang  5 , Paula Tanabe  5 , Nirmish Shah  6 , Faith S Luyster  7 , Charity Oyedeji  6   8 , John J Strouse  6   8 , Harvey J Cohen  3 , Nathan A Kimbrel  2   4 , Jean C Beckham  2   4 , Mitchell R Knisely  5 , Marilyn J Telen  6 , Allison E Ashley-Koch  1 ; VA Mid-Atlantic MIRECC Workgroup
Collaborators, Affiliations
Comparative Study

Black Americans With Sickle Cell Disease (SCD) Demonstrate Accelerated Epigenetic Pace of Aging Compared to Black Americans Without SCD

Melanie E Garrett et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Background: Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared with individuals without SCD.

Methods: We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD.

Results: SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared with the veterans without SCD, whereby SCD patients were aging ≈0.7 months more per year than those without SCD (p = 4.49 × 10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with posttraumatic stress disorder from the non-SCD group (p = 2.18 × 10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p = 1.61 × 10-10).

Conclusions: These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.

Keywords: Chronic disease pathology; DNA methylation; Hemoglobinopathy.

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Conflict of interest statement

N.S. is a consultant for Global Blood Therapeutics (GBT)/Pfizer, Forma, Agios, Vertex, and bluebird bio, is a speaker for GBT/Pfizer and Alexion, and performs research on GBT/Pfizer. P.T. is a consultant for CSL Behring. J.S. is a consultant for Disc Medicine and Editas Medicine and has research funding from Agios Pharmaceuticals. All other authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Epigenetic pace of aging in sickle cell disease (SCD) as measured by DunedinPACE. Blue bars and lines (shifted right) depict SCD patients; red bars and lines (shifted left) depict non-Hispanic Black (NHB) veterans.
Figure 2.
Figure 2.
Age-adjusted DunedinPACE mean scores for 5 subsets of the data set: All non-Hispanic Black (NHB) veterans, NHB veterans without posttraumatic stress disorder (PTSD), NHB veterans with PTSD, all sickle cell disease (SCD) patients, and SCD patients with HbSS or HbSβ0 genotypes. SCD patients have significantly higher DunedinPACE scores compared with all NHB veterans (p = 4.49 × 10−8), NHB veterans without PTSD (p = 2.18 × 10−9), and NHB veterans with PTSD (p = 5.02 × 10−5). SCD patients with HbSS or HbSβ0 genotypes have significantly higher DunedinPACE scores compared with all NHB veterans (4.2 × 10−9), NHB veterans without PTSD (p = 1.61 × 10−10), and NHB veterans with PTSD (5.94 × 10−6).
Figure 3.
Figure 3.
Age-adjusted DunedinPACE mean scores depicting a trending cohort*sex interaction (p = .073). NHB = non-Hispanic Black; SCD = sickle cell disease.
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